Construction of a 3-year risk prediction model for developing diabetes in patients with pre-diabetes.

Introduction: To analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the 3-year risk of developing diabetes in patients with PreDM. Methods: Subjects who were diagnosed with new-onset PreDM at the Physical Examination Center of the First Affiliated Hospital of Soochow University from October 1, 2015 to May 31, 2023 and completed the 3-year follow-up were selected as the study population. Data on gender, age, body mass index (BMI), waist circumference, etc. were collected. After 3 years of follow-up, subjects were divided into a diabetes group and a non-diabetes group. Baseline data between the two groups were compared. A prediction model based on logistic regression was established with nomogram drawn. The calibration was also depicted. Results: Comparison between diabetes group and non-diabetes group: Differences in 24 indicators including gender, age, history of hypertension, fatty liver, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, etc. were statistically significant between the two groups (P<0.05). Differences in smoking, creatinine and platelet count were not statistically significant between the two groups (P>0.05). Logistic regression analysis showed that ageing, elevated BMI, male gender, high fasting blood glucose, increased LDL-C, fatty liver, liver dysfunction were risk factors for progression from PreDM to diabetes within 3 years (P<0.05), while HDL-C was a protective factor (P<0.05). The derived formula was: In(p/1-p)=0.181×age (40-54 years old)/0.973×age (55-74 years old)/1.868×age (≥75 years old)-0.192×gender (male)+0.151×blood glucose-0.538×BMI (24-28)-0.538×BMI (≥28)-0.109×HDL-C+0.021×LDL-C+0.365×fatty liver (yes)+0.444×liver dysfunction (yes)-10.038. The AUC of the model for predicting progression from PreDM to diabetes within 3 years was 0.787, indicating good predictive ability of the model. Conclusions: The risk prediction model for developing diabetes within 3 years in patients with PreDM constructed based on 8 influencing factors including age, BMI, gender, fasting blood glucose, LDL-C, HDL-C, fatty liver and liver dysfunction showed good discrimination and calibration.

Association between heme oxygenase-1 and hyperlipidemia in pre-diabetic patients: a cross-sectional study.

Background: Although the importance and benefit of heme oxygenase-1 (HO-1) in diabetes rodent models has been known, the contribution of HO-1 in the pre-diabetic patients with hyperlipidemia risk still remains unclear. This cross-sectional study aims to evaluate whether HO-1 is associated with hyperlipidemia in pre-diabetes. Methods: Serum level of HO-1 was detected using commercially available ELISA kit among 1,425 participants aged 49.3-63.9 with pre-diabetes in a multicenter Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal (REACTION) prospective observational study. Levels of total cholesterol (TC) and triglyceride (TG) were measured and used to defined hyperlipidemia. The association between HO-1 and hyperlipidemia was explored in different subgroups. Result: The level of HO-1 in pre-diabetic patients with hyperlipidemia (181.72 ± 309.57 pg/ml) was obviously lower than that in pre-diabetic patients without hyperlipidemia (322.95 ± 456.37 pg/ml). High level of HO-1 [(210.18,1,746.18) pg/ml] was negatively associated with hyperlipidemia (OR, 0.60; 95% CI, 0.37-0.97; p = 0.0367) after we adjusted potential confounding factors. In subgroup analysis, high level of HO-1 was negatively associated with hyperlipidemia in overweight pre-diabetic patients (OR, 0.50; 95% CI, 0.3-0.9; p = 0.034), especially in overweight women (OR, 0.42; 95% CI, 0.21-0.84; p = 0.014). Conclusions: In conclusion, elevated HO-1 level was negatively associated with risk of hyperlipidemia in overweight pre-diabetic patients, especially in female ones. Our findings provide information on the exploratory study of the mechanism of HO-1 in hyperlipidemia, while also suggesting that its mechanism may be influenced by body weight and gender.

Role of secreted frizzled-related protein 4 in prediabetes and type 2 diabetes: a cross sectional study.

BACKGROUND: Type 2 diabetes (T2D) has become an epidemic. Delays in diagnosis and as a consequent late treatment has resulted in high prevalence of complications and mortality. Secreted frizzled-related protein 4 (SFRP4), has been recently identified as a potential early biomarker of T2D related to obesity, due to its association with low grade inflammation in adipose tissue and impaired glucose metabolism. We aimed to evaluate the role of SFRP4 in prediabetes and T2D in a Mexican population. METHODS: This was a cross-sectional study that included 80 subjects with T2D, 50 subjects with prediabetes and 50 healthy individuals. Fasting SFRP4 and insulin concentrations were measured by ELISA. Human serum IL-10, IL-6, IL-1ß and IL-8 levels were quantified by flow cytometry. Genotyping was performed by TaqMan® probes. RESULTS: Prediabetes and T2D patients had significantly higher SFRP4 levels than controls (P < 0.05). In turn, prediabetes subjects had higher SFRP4 concentrations than control subjects (P < 0.05). Additionally, the prediabetes and T2D groups had higher concentrations of proinflammatory molecules such as IL-6, IL-1ß and IL-8, and lower concentrations of IL-10, an anti-inflammatory cytokine, than controls (P < 0.001). The serum SFRP4 concentrations were positively correlated with parameters that are elevated in prediabetes and T2D states, such as, HbA1c and homeostasis model assessment insulin resistance (HOMA-IR), (r = 0.168 and 0.248, respectively, P < 0.05). Also, serum SFRP4 concentrations were positively correlated with concentrations of pro-inflammatory molecules (CRP, IL-6, IL-1ß and IL-8) and negatively correlated with the anti-inflammatory molecule IL-10, even after adjusting for body mass index and age (P < 0.001). The genetic variant rs4720265 was correlated with low HDL concentrations in T2D (P < 0.05). CONCLUSIONS: SFRP4 correlates positively with the stage of prediabetes, suggesting that it may be an early biomarker to predict the risk of developing diabetes in people with high serum concentrations of SFRP4, although further longitudinal studies are required.

Prediction of Diabetes and Prediabetes among the Saudi Population Using a Non-Invasive Tool (AUSDRISK).

Background and Objectives: Screening for type 2 diabetes mellitus (DM2) aims to identify asymptomatic individuals who may be at a higher risk, allowing proactive interventions. The objective of this study was to predict the incidence of DM2 and prediabetes in the Saudi population over the next five years. Materials and Methods: The study was conducted in the Aseer region through August 2023 using a cross-sectional survey for data collection. A multistage stratified random sampling technique was adopted, and data were collected through face-to-face interviews using the validated Arabic version of the Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK). Results: In total, 652 individuals were included in the study. Their mean age was 32.0 ± 12.0 years; 53.8% were male, 89.6% were from urban areas, and 55.8% were single. There were statistically significant differences between males and females in AUSDRISK items, including age, history of high blood glucose, use of medications for high blood pressure, smoking, physical activity, and measurements of waist circumference (p < 0.05). Based on AUSDRISK scores, 46.2% of the included participants were predicted to develop impaired glucose tolerance within the coming five years (65.8% among females vs. 23.6%), and 21.9% were predicted to develop DM2 (35.6% among males vs. 6.0% among females); this difference was statistically significant (p = 0.0001). Conclusions: Urgent public health action is required to prevent the increasing epidemic of DM2 in Saudi Arabia.

MAFLD and glomerular hyperfiltration in subjects with normoglycemia, prediabetes and type 2 diabetes: A cross-sectional population study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD, 2020 diagnostic criteria) and glomerular hyperfiltration share common risk factors, including obesity, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, and hypertension. AIMS: To assess the prevalence of MAFLD and its association with glomerular hyperfiltration and age-related worsening of kidney function in subjects with normoglycemia, prediabetes and type 2 diabetes mellitus (T2DM). METHODS: We analysed data recorded during occupational health visits of 125,070 Spanish civil servants aged 18-65 years with a de-indexed glomerular filtration rate (GFR) estimated with the chronic-kidney-disease-epidemiological (CKD-EPI) equation (estimated glomerular filtration rate [eGFR]) ≥60 mL/min. Subjects were categorised according to fasting plasma glucose levels <100 mg/dL (normoglycemia), ≥100 and ≤ 125 mg/dL (prediabetes), or ≥126 mg/dL and/or antidiabetic treatment (T2DM). The association between MAFLD and glomerular hyperfiltration, defined as a de-indexed eGFR above the age- and gender-specific 95th percentile, was assessed by multivariable logistic regression. RESULTS: In the whole study group, MAFLD prevalence averaged 19.3%. The prevalence progressively increased from 14.7% to 33.2% and to 48.9% in subjects with normoglycemia, prediabetes and T2DM, respectively (p < 0.001 for trend). Adjusted odds ratio (95% CI) for the association between MAFLD and hyperfiltration was 9.06 (8.53-9.62) in the study group considered as a whole, and 8.60 (8.03-9.21), 9.52 (8.11-11.18) and 8.31 (6.70-10.30) in subjects with normoglycemia, prediabetes and T2DM considered separately. In stratified analyses, MAFLD amplified age-dependent eGFR decline in all groups (p < 0.001). CONCLUSIONS: MAFLD prevalence increases across the glycaemic spectrum. MAFLD is significantly associated with hyperfiltration and amplifies the age-related eGFR decline.

Determinants of serious health outcome-free status in middle-aged and older people with dysglycaemia: Exploratory analysis of the ORIGIN trial.

AIM: To assess clinical and biochemical measurements that can identify people with dysglycaemia (i.e. diabetes or pre-diabetes) who remain free of serious outcomes during follow-up. MATERIALS AND METHODS: We conducted exploratory analyses using data from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) study to identify independent determinants of outcome-free status in 12 537 middle-aged and older adults with prediabetes and early type 2 diabetes from 40 countries. Serious outcome-free status was defined as the absence of major cardiovascular outcomes, kidney or retinal outcomes, peripheral artery disease, dementia, cancer, any hospitalization, or death during follow-up. RESULTS: In total, 3328 (26.6%) participants remained free of serious outcomes during a median follow-up of 6.2 years (IQR 5.8, 6.7). Independent clinical determinants of outcome-free status included younger age, female sex, non-White ethnicity, shorter diabetes duration, absence of previous cardiovascular disease, current or former smokers, higher grip strength, Mini-Mental State Examination score, and ankle-brachial index, lower body mass index and kidney disease index, and non-use of renin-angiotensin system drugs and beta-blockers. In a subset of 8401 people with baseline measurements of 238 biomarkers, growth differentiation factor 15, kidney injury molecule-1, N-terminal pro-brain natriuretic peptide, uromodulin, C-reactive protein, factor VII and ferritin were independent determinants. The combination of clinical determinants and biomarkers best identified participants who remained outcome-free (C-statistics 0.71, 95% confidence interval 0.70-0.73; net reclassification improvement 0.55, 95% confidence interval 0.48-0.58). CONCLUSIONS: A set of routinely measured clinical characteristics and seven protein biomarkers identify middle-aged and older people with prediabetes or early type 2 diabetes as least likely to experience serious outcomes during follow-up.

Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study.

BACKGROUND: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR). METHODS: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min. RESULTS: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable. CONCLUSIONS: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.

Metabolic Alteration Bridging the Prediabetic State and Colorectal Cancer.

Prediabetes and colorectal cancer (CRC) represent compelling health burdens responsible for high mortality and morbidity rates, sharing several modifiable risk factors. It has been hypothesized that metabolic abnormalities linking prediabetes and CRC are hyperglycemia, hyperinsulinemia, and adipokines imbalance. The chronic stimulation related to these metabolic signatures can favor CRC onset and development, as well as negatively influence CRC prognosis. To date, the growing burden of prediabetes and CRC has generated a global interest in defining their epidemiological and molecular relationships. Therefore, a deeper knowledge of the metabolic impairment determinants is compelling to identify the pathological mechanisms promoting the onset of prediabetes and CRC. In this scenario, this review aims to provide a comprehensive overview on the metabolic alterations of prediabetes and CRC as well as an overview of recent preventive and therapeutic approaches for both diseases, focusing on the role of the metabolic state as a pivotal contributor to consider for the development of future preventive and therapeutic strategies.

Association between glycemic status and the risk of gastric cancer in pre/peri-and postmenopausal women: A nationwide cohort study.

PURPOSE: This study aimed to assess the correlation between glycemic status (prediabetes and type 2 diabetes mellitus) and the risk of gastric cancer according to menopausal status. METHODS: A total of 982,559 pre/peri-menopausal and 1445,419 postmenopausal women aged ≥ 40, who underwent the Korean national health screening in 2009, were included and followed up until 2018. Hazard ratio (HR) and 95% confidence interval (CI) were calculated for development of gastric cancers according to hyperglycemic status in both groups using Cox proportional hazards models. RESULTS: Over a mean follow-up period of 8.3 years, 3259 (0.33%) pre/peri-menopausal women and 13,245 (0.92%) postmenopausal women were diagnosed with gastric cancer. In postmenopausal women, only diabetes mellitus conferred a higher risk of gastric cancer compared to normal glycemic status (HR, 1.15; 95% CI, 1.09-1.20), with an increasing trend of gastric cancers from prediabetes to diabetes (P for trend < 0.001) observed regardless of menopausal status. Obesity, smoking, and heavy alcohol consumption was associated with increased gastric cancer risk mainly in the postmenopausal period. CONCLUSIONS: The risk of gastric cancer escalates with deteriorating glycemic status in a dose-response manner. Diabetes mellitus is linked with an elevated risk of gastric cancer in postmenopausal women.

Undiagnosed type 2 diabetes is common - intensified screening of established risk groups is imperative in Sweden: the SDPP cohort.

BACKGROUND: Undiagnosed type 2 diabetes (T2D) is a global problem. Current strategies for diagnosis in Sweden include screening individuals within primary healthcare who are of high risk, such as those with hypertension, obesity, prediabetes, family history of diabetes, or those who smoke daily. In this study, we aimed to estimate the proportion of individuals with undiagnosed T2D in Stockholm County and factors associated with T2D being diagnosed by healthcare. This information could improve strategies for detection. METHODS: We used data from the Stockholm Diabetes Prevention Programme (SDPP) cohort together with information from national and regional registers. Individuals without T2D aged 35-56 years at baseline were followed up after two ten-year periods. The proportion of diagnosed T2D was based on register information for 7664 individuals during period 1 and for 5148 during period 2. Undiagnosed T2D was assessed by oral glucose tolerance tests at the end of each period. With logistic regression, we analysed factors associated with being diagnosed among individuals with T2D. RESULTS: At the end of the first period, the proportion of individuals with T2D who had been diagnosed with T2D or not was similar (54.0% undiagnosed). At the end of the second period, the proportion of individuals with T2D was generally higher, but they were less likely to be undiagnosed (43.5%). The likelihood of being diagnosed was in adjusted analyses associated with overweight (OR=1.85; 95% CI 1.22-2.80), obesity (OR=2.73; 95% CI 1.76-4.23), higher fasting blood glucose (OR=2.11; 95% CI 1.67-2.66), and self-estimated poor general health (OR=2.42; 95% CI 1.07-5.45). Socioeconomic factors were not associated with being diagnosed among individuals with T2D. Most individuals (>71%) who developed T2D belonged to risk groups defined by having at least two of the prominent risk factors obesity, hypertension, daily smoking, prediabetes, or family history of T2D, including individuals with T2D who had not been diagnosed by healthcare. CONCLUSIONS: Nearly half of individuals who develop T2D during 10 years in Stockholm County are undiagnosed, emphasizing a need for intensified screening of T2D within primary healthcare. Screening can be targeted to individuals who have at least two prominent risk factors.

Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes.

OBJECTIVE: Prediabetes and lifestyle factors have been associated with the risks of multiple adverse outcomes, but the effect of a healthy lifestyle on prediabetes-related complications remains unknown. We aimed to investigate whether the risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) among individuals with prediabetes can be offset by a broad combination of healthy lifestyle factors. METHODS: This prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 6 was created with 1 point for each of the 6 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, no overweight or obese, and adequate sleep duration. T2DM, CVD, and CKD were ascertained during a median follow-up of 14 years. Cox proportional hazard regression models were used to estimate the associations. Sensitivity analyses were performed to test the robustness of the results. RESULTS: We included 202,993 participants without T2DM, CVD, and CKD at baseline (mean age 55.5 years [SD 8.1]; 54.7% were women). Among these participants, 6,745, 16,961, and 6,260 participants eventually developed T2DM, CVD, and CKD, respectively. Compared with the participants with normoglycaemia, those with prediabetes showed a higher risk of these adverse outcomes. In addition, those prediabetic participants with a lifestyle score of 0-1 had a significantly higher risk of T2DM (hazard ratio [HR] 16.73, 95% CI 14.24, 19.65), CVD (HR 1.96, 95% CI 1.74, 2.21), and CKD (HR 1.92, 95% CI 1.58, 2.34) compared with those with no prediabetes and a score of 5-6. Moreover, among the participants with prediabetes, the HRs for T2DM, CVD, and CKD comparing a lifestyle score of 5-6 versus 0-1 decreased to 0.43 (95% CI 0.36, 0.51), 0.52 (95% CI 0.44, 0.62), and 0.60 (95% CI 0.46, 0.79), respectively. CONCLUSIONS: Combined healthy lifestyle factors were associated with a significantly lower risk of multiple adverse outcomes, including T2DM, CVD, and CKD. This indicates that prioritising multifactorial approaches to behavioural lifestyle modification is crucial for preventing and postponing the development of complications related to prediabetes.

The associations of risk of cardiovascular disease with development stages of diabetes in Chinese population: findings from a retrospective cohort study in QuZhou city.

BACKGROUND: Risk analysis is an important area of research in diabetes and cardiovascular disease (CVD), both of which have significant global health burdens. Although there is evidence that patients with prediabetes and diabetes mellitus may have an increased risk of CVD, few studies have been conducted in mainland China. METHODS: This retrospective cohort study utilized data from the Quzhou City Resident Health Information System and the Zhejiang Province Chronic Disease Surveillance System in China. Prediabetes and diabetes mellitus were the exposure interests, and the outcome event was defined as the onset of cardiovascular and cerebrovascular disease (including coronary heart disease and stroke). The start date of the study was January 1, 2015, and the follow-up deadline was December 31, 2020. Multivariate Cox proportional hazard model were used to assess the associations among prediabetes, diabetes, and CVD risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Our study used follow-up time as the time scale, while adjusting for age, sex, physical activity, smoking, alcohol consumption, BMI in the models Sensitivity analyses were conducted to assess the stability of the results, by excluding participants who smoked and drank alcohol, participants who developed CVD in the first year of follow-up. RESULTS: In total, 138,970 participants were included in our study, with a mean follow-up of 5.8 years. The mean age of the participants was 58.82 ± 14.44 years, with 42.79% (n = 59,466) males and 57.21% (n = 79,504) females. During the study period 4357 cases of CVD were recorded. Participants with prediabetes (P = 0.003) and diabetes (P < 0.001) had a higher risk of CVD than those who were Normal (HR [95% CI]: 1.14 [1.05-1.24]; 1.68 [1.55-1.81], respectively). Prediabetes and patients living with diabetes had a 14% and 68% increased risk of CVD, respectively. The results of the sensitivity analyses were consistent with those of the main analyses after excluding those who developed CVD within one year of follow-up and those who were concurrent smokers or alcohol drinkers. CONCLUSIONS: Our research found that prediabetes is significantly associated with the risk of diabetes and CVD.

The prognostic value of the stress hyperglycemia ratio for all-cause and cardiovascular mortality in patients with diabetes or prediabetes: insights from NHANES 2005-2018.

BACKGROUND: The Stress hyperglycemia ratio (SHR) is a novel marker reflecting the true acute hyperglycemia status and is associated with clinical adverse events. The relationship between SHR and mortality in patients with diabetes or prediabetes is still unclear. This study aimed to investigate the predictive value of the SHR for all-cause and cardiovascular mortality in patients with diabetes or prediabetes. METHODS: This study included 11,160 patients diagnosed with diabetes or prediabetes from the National Health and Nutrition Examination Survey (2005-2018). The study endpoints were all-cause and cardiovascular mortality, and morality data were extracted from the National Death Index (NDI) up to December 31, 2019. Patients were divided into SHR quartiles. Cox proportion hazards regression was applied to determine the prognostic value of SHR. Model 1 was not adjusted for any covariates. Model 2 was adjusted for age, sex, and race. Model 3 was adjusted for age, sex, race, BMI, smoking status, alcohol use, hypertension, CHD, CKD, anemia, and TG. RESULTS: During a mean follow-up of 84.9 months, a total of 1538 all-cause deaths and 410 cardiovascular deaths were recorded. Kaplan-Meier survival analysis showed the lowest all-cause mortality incidence was in quartile 3 (P < 0.001). Multivariate Cox regression analyses indicated that, compared to the 1st quartile, the 4th quartile was associated with higher all-cause mortality (model 1: HR = 0.89, 95% CI 0.74-10.7, P = 0.226; model 2: HR = 1.24, 95% CI 1.03-1.49, P = 0.026; model 3: HR = 1.30, 95% CI 1.08-1.57, P = 0.006). The 3rd quartile was associated with lower cardiovascular mortality than quartile 1 (model 1: HR = 0.47, 95% CI 0.32-0.69, P < 0.001; model 2: HR = 0.66, 95% CI 0.45-0.96, P = 0.032; model 3: HR = 0.68, 95% CI 0.46-0.99, P = 0.049). There was a U-shaped association between SHR and all-cause mortality and an L-shaped association between SHR and cardiovascular mortality, with inflection points of SHR for poor prognosis of 0.87 and 0.93, respectively. CONCLUSION: SHR is related to all-cause and cardiovascular mortality in patients with diabetes or prediabetes. SHR may have predictive value in those patients.

Associations of glycosylated hemoglobin, pre-diabetes, and type 2 diabetes with incident lung cancer: A large prospective cohort study.

BACKGROUND: The association of pre-diabetes and type 2 diabetes (T2D) with incident lung cancer is uncertain, and the incident risk across the glycemic spectrum is unclear. We aimed to explore the associations of glycosylated hemoglobin (HbA1c), pre-diabetes, and T2D with incident lung cancer in a large prospective cohort. METHODS: Leveraging a total of 210,779 cancer-free adults recruited in the UK Biobank between 2006 and 2010. We performed multivariable Cox proportional hazards models and restricted cubic spline methods to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations of HbA1c, pre-diabetes, and T2D with incident lung cancer. RESULTS: During a median follow-up of 11.06 years, 1738 incident lung cancer cases were ascertained. The incidence of lung cancer was 20% higher among people with diabetes (HR: 1.20, 95% CI: 1.02 to 1.42) and 38% higher among people with pre-diabetes (HR: 1.38, 95% CI: 1.15 to 1.65). After dividing people with diabetes by whether taking antidiabetic medications, the incidence was 28% higher among people with diabetes without medications (HR: 1.28, 95% CI: 1.02 to 1.61) and 15% higher among people with diabetes with medications (HR: 1.15, 95% CI: 0.93 to 1.41). The increased risk of incident lung cancer for each standard deviation (6.45 mmol/mol) increase in HbA1c was more pronounced across HbA1c values of 32-42 mmol/mol (HR: 1.37, 95% CI: 1.18 to 1.59). The risk was more pronounced among participants <60 years. CONCLUSIONS: Pre-diabetes and T2D are associated with an increased incidence of lung cancer. The increased risk of incident lung cancer is more pronounced across HbA1c values of 32-42 mmol/mol, which are currently considered normal values.

Does metformin reduce the risk of cancer in obesity and diabetes? A systematic review and meta-analysis.

AIM: To evaluate the effect of metformin on cancer incidence in subjects with overweight/obesity and/or prediabetes/diabetes. MATERIALS AND METHODS: We searched MEDLINE, Embase and CENTRAL for randomized controlled trials (RCTs) in adults with overweight/obesity and/or prediabetes/diabetes that compared metformin to other interventions for ≥24 weeks. Independent reviewers selected and extracted data including population and intervention characteristics and new diagnoses of cancer. We used the RoB 2.0 risk-of-bias tool and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework to assess risk of bias and certainty of evidence. RESULTS: From 14 895 records after removal of duplicates, 27 trials were included, providing a total of 10 717 subjects in the metformin group and 10 003 in the control group, with 170 and 208 new cases of cancer, respectively. Using a random-effects model, the relative risk was 1.07 (95% confidence interval 0.87-1.31), with similar results in subgroup analyses by study duration or effect of control intervention on weight. Risk of bias in most studies was low, and no evidence of publication bias was found. Trial sequential analysis provided evidence that the cumulative sample size was large enough to exclude a significant effect of metformin on cancer incidence. CONCLUSIONS: Metformin did not reduce cancer incidence in RCTs involving subjects with overweight/obesity and/or prediabetes/diabetes.

Prediabetes remission after bariatric surgery: a 4-years follow-up study.

BACKGROUND: Bariatric surgery leads to weight loss and to cardiometabolic risk improvement. Although prediabetes remission after bariatric surgery is biologically plausible, data on this topic is scarce. We aimed to assess prediabetes remission rate and clinical predictors of remission in a 4 year follow up period. METHODS: Observational longitudinal study including patients with obesity and prediabetes who had undergone bariatric surgery in our centre. Prediabetes was defined as having a baseline glycated haemoglobin (A1c) between 5.7% and 6.4% and absence of anti-diabetic drug treatment. We used logistic regression models to evaluate the association between the predictors and prediabetes remission rate. RESULTS: A total of 669 patients were included, 84% being female. The population had a mean age of 45.4 ± 10.1 years-old, body mass index of 43.8 ± 5.7 kg/m2, and median A1c of 5.9 [5.8, 6.1]%. After bariatric surgery, prediabetes remission rate was 82%, 73%, 66%, and 58%, respectively in the 1st, 2nd, 3rd, and 4th years of follow-up. Gastric sleeve (GS) surgery was associated with higher prediabetes remission rate than Roux-en-Y gastric bypass surgery in the 3rd year of follow-up. Men had a higher remission rate than women, in the 1st and 3nd years of follow-up in the unadjusted analysis. Younger patients presented a higher remission rate comparing to older patients in the 3rd year of follow-up. CONCLUSION: We showed a high prediabetes remission rate after bariatric surgery. The remission rate decreases over the follow-up period, although most of the patients maintain the normoglycemia. Prediabetes remission seems to be more significant in patients who had undergone GS, in male and in younger patients.

[FINDRISC as screening for detection of prediabetes and unknown type 2 diabetes]. / Evaluación del puntaje FINDRISC para detección de prediabetes y diabetes tipo 2 sin diagnóstico.

INTRODUCTION: It is fundamental to put into practice preventive and early population diagnosis actions to detect people at risk for developing Type 2 diabetes (T2D). The aim of this study was to evaluate the FINDRISC score performance as screening method to detect prediabetes and unknown T2D in municipal workers. METHODS: descriptive epidemiological and crosssectional study from 10/21 to 03/22. People suffering from a severe illness, pregnant or were already receiving drugs that modify blood glucose, were excluded. Participants completed the FINDRISC and performed an oral glucose tolerance test (OGTT). The performance of the FINDRISC was determined by calculating sensitivity, specificity, and area under the curve (AUC-ROC). The Youden's J statistic index was used to define the optimal cutoff point. RESULTS: 148 subjects between the ages of 18-65 were admitted, with a mean age of 42,9 ± 11,8, the 69% being males. The frequency of unknown T2D was of 3.3% (n = 5) and frequency of prediabetes was of 12.2% (n = 18). The mean of FINDRISC score was of 10.0 ± 4.8. The optimal cutoff point was ≥ 13 (sensitivity = 65.2%, Specificity = 74.4%) and the AUC-ROC 0.76 (IC95%: 0.66-0.86). CONCLUSION: The FINDRISC proved to be an effective method for identifying people with undiagnosed T2D and prediabetes with a cut-off point of 13 in the population, place, and study period.

Introducción: Es fundamental poner en práctica acciones preventivas y de diagnóstico poblacional precoz para detectar a las personas en riesgo de desarrollar Diabetes tipo 2 (DT2). El objetivo del trabajo fue evaluar el desempeño del score FINDRISC como método de cribado para detectar prediabetes y DT2 sin diagnostico en trabajadores municipales. Métodos: Estudio epidemiológico, descriptivo de corte transversal desde 10/21 al 3/22. Ingresaron voluntarios mayores a 18 años sin diagnóstico previo de DT2, se excluyó quienes padecían una enfermedad aguda, embarazadas o que realizaban tratamiento con medicamentos que modifiquen la glucemia. Los participantes completaron el FINDRISC y realizaron una Prueba Oral de Tolerancia a la Glucosa (POTG). El desempeño se determinó mediante el cálculo de la sensibilidad (S), especificidad (E), y el área bajo la curva (AUC-ROC). Se utilizó un índice de Youden para definir el punto de corte óptimo. Resultados: Ingresaron 148 personas, entre 18-67 años, con media de edad 42.9 ± 11.8 años, el 68.9% de sexo masculino. La frecuencia de DT2 sin diagnóstico fue del 3.3% (n = 5) y de prediabetes del 12.2% (n = 18). El promedio de puntos de FINDRISC fue de 10.0 ± 4.8. El punto de corte optimo fue ≥ 13 (S = 65.2% y E = 74.4%) y el AUC-ROC 0.76 (IC95%: 0.66-0.86). Conclusión: El FINDRISC demostró ser un método eficaz para identificar personas con DT2 y prediabetes con punto de corte 13 en la población, lugar y periodo de estudio.

Changes in Isoleucine, Sarcosine, and Dimethylglycine During OGTT as Risk Factors for Diabetes.

CONTEXT: Current metabolomics studies in diabetes have focused on the fasting state, while only a few have addressed the satiated state. OBJECTIVE: We combined the oral glucose tolerance test (OGTT) and metabolomics to examine metabolite-level changes in populations with different glucose tolerance statuses and to evaluate the potential risk of these changes for diabetes. METHODS: We grouped participants into those with normal glucose tolerance (NGT), impaired glucose regulation (IGR), and newly diagnosed type 2 diabetes (NDM). During the OGTT, serum was collected at 0, 30, 60, 120, and 180 minutes. We evaluated the changes in metabolite levels during the OGTT and compared metabolic profiles among the 3 groups. The relationship between metabolite levels during the OGTT and risk of diabetes and prediabetes was analyzed using a generalized estimating equation (GEE). The regression results were adjusted for sex, body mass index, fasting insulin levels, heart rate, smoking status, and blood pressure. RESULTS: Glucose intake altered metabolic profile and induced an increase in glycolytic intermediates and a decrease in amino acids, glycerol, ketone bodies, and triglycerides. Isoleucine levels differed between the NGT and NDM groups and between the NGT and IGR groups. Changes in sarcosine levels during the OGTT in the diabetes groups were opposite to those in glycine levels. GEE analysis revealed that during OGTT, isoleucine, sarcosine, and acetic acid levels were associated with NDM risks, and isoleucine and acetate levels with IGR risks. CONCLUSION: Metabolic profiles differ after glucose induction in individuals with different glucose tolerance statuses. Changes in metabolite levels during OGTT are potential risk factors for diabetes development.

Prediabetes and Associated Risk of Cardiovascular Events and Chronic Kidney Disease Among Adult Survivors of Childhood Cancer in the St Jude Lifetime Cohort.

PURPOSE: Little is known about the prevalence of prediabetes and associated risk of cardiovascular events and chronic kidney disease (CKD) with this reversable condition in survivors. METHODS: Prevalence of prediabetes (fasting plasma glucose 100-125 mg/dL or hemoglobin A1c 5.7%-6.4%) and diabetes was clinically assessed in 3,529 adults ≥5 years from childhood cancer diagnosis and 448 controls stratified by age. Cox proportional hazards regression estimated progression from prediabetes to diabetes, and risk of future cardiac events, stroke, CKD, and death. RESULTS: Among survivors, median age 30 years (IQR, 18-65), and the prevalence of prediabetes was 29.2% (95% CI, 27.7 to 30.7) versus 18.1% (14.5 to 21.6) in controls and of diabetes was 6.5% (5.7 to 7.3) versus 4.7% (2.7 to 6.6). By age 40-49 years, more than half of the survivors had prediabetes (45.5%) or diabetes (14.0%). Among 695 survivors with prediabetes and longitudinal follow-up, 68 (10%; median follow-up, 5.1 years) progressed to diabetes. After adjustment for demographic factors and body composition, risk of progression was associated with radiation exposure to the pancreatic tail ≥10 Gy (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.8]) and total-body irradiation (4.4 [1.5 to 13.1]). Compared with survivors with normal glucose control, adjusting for relevant treatment exposures, those with prediabetes were at increased risk of future myocardial infarction (HR, 2.4 [95% CI, 1.2 to 4.8]) and CKD (2.9 [1.04 to 8.15]), while those with diabetes were also at increased risk of future cardiomyopathy (3.8 [1.4 to 10.5]) or stroke (3.4 [1.3 to 8.9]). CONCLUSION: Prediabetes is highly prevalent in adult survivors of childhood cancer and independently associated with an increased risk of future cardiovascular and kidney complications. Prediabetes, a modifiable risk factor among childhood cancer survivors, represents a new target for intervention that may prevent subsequent morbidity and mortality.

Association between prediabetes and breast cancer: a comprehensive meta-analysis.

BACKGROUND: Breast cancer accounts for up to 30% of cancer cases in women in the US. Diabetes mellitus has been recognized as a risk factor for breast cancer. Some studies have suggested that prediabetes may also be associated with breast cancer whereas other studies have shown no or an inverse association; thus, we conducted a meta-analysis to assess the risk of breast cancer in prediabetes. METHODS: We searched PubMed/Medline, EMBASE, Google Scholar, and Scopus to identify studies that reported breast cancer risks in patients having prediabetes compared to normoglycemic patients. Binary random-effects model was used to calculate a pooled odds ratio (OR) with 95% confidence intervals. I2 statistics were used to assess heterogeneity. Leave-one-out sensitivity analysis and subgroup analyses were performed. RESULTS: We analyzed 7 studies with 24,586 prediabetic and 224,314 normoglycemic individuals (783 and 5739 breast cancer cases, respectively). Unadjusted odds ratio (OR) for breast cancer was 1.45 (95% CI = 1.14, 1.83); adjusted OR was 1.19 (95% CI = 1.07, 1.34) in prediabetes. Subgroup analysis revealed a higher breast cancer risk in individuals aged less than 60 years (OR = 1.86, 95% CI = 1.39, 2.49) than in those aged 60 years or more (OR = 1.07, 95% CI = 0.97, 1.18). Subgroup analysis by median follow-up length indicated a higher risk of breast cancer for follow-ups of less than or equal to 2 years (OR = 2.34, 95% CI = 1.85, 2.95) than in those of over 10 years (OR = 1.1, 95% CI = 0.99, 1.23) and 6 to 10 years (OR = 1.03, 95% CI = 0.88, 1.21). CONCLUSIONS: In conclusion, individuals with prediabetes have higher risk of developing breast cancer than those with normoglycemia, especially younger prediabetes patients. These individuals may benefit from early identification, monitoring, and interventions to reverse prediabetes.